Gene Therapy Gives Hope in Virulent Form of Cancer

Stephen Dixon, 57, of Nashville, Tenn., has watched his tumors from melanoma shrink on the experimental gene therapy called RO5185426.

Courtesy Stephen Dixon

Melanoma researchers are known to be a jaded bunch.

Despite years of research, the last significant new treatment for the severe form of skin cancer came out in 1992 -- and only 5 percent to 10 percent of cancer patients get any lasting results with that treatment.

The best doctors have been able to offer patients has been experimental medicine, "because there are no right answers," on how to treat melanoma that has spread to other organs, Dr. Anna Pavlik, director of the melanoma program at the New York University Cancer Institute.

But in 2008, patients enrolled in a clinical trial of an experimental drug called PLX4032 started to get better. Much better.

"I've never seen anything like this," said Dr. Jeffry Sosman, principle investigator of the recently completed phase II study the new drug. "I had patients who were in extreme pain and within a week or so, came to the office off of pain medicine."

Sosman said that drug, which is now known as RO5185426 is designed to hit the "Achilles' heel" of a tumor. The drug works by blocking the effects of the so-called BRAF genetic mutation discovered to be in melanoma tumors through the human genome project. Turn off the gene, and it will stop sending signals to the cells to grow uncontrollably.

About 70 percent to 80 percent of patients with the mutation saw their tumors regress, often by about 50 percent within months of trying the medicine, Sosman said. And unlike chemotherapy, which often works for six months or so before tumors grow again, most of the patients who tried RO5185426 are still waiting for the other shoe to drop.

Twelve years earlier doctors removed malignant mole on his neck along with a section of his skin. For a decade, check-ups showed no sign of cancer and Dixon was told he go on without appointments, cancer-free. Then somewhere from that area, the cancer grew again under his skin.

"I was having night sweats, and I didn't understand why," said Dixon. "And rather than going to my primary care doctor, I went to my oncologist and he found it."

When he started RO5185426 10 months ago, the melanoma in his neck had spread to his lymph nodes and attacked his one of his adrenal glands.

Dixon said he already knew the prognosis for this type of cancer. Only 16 percent of people with his diagnosis survive for 5 years. So Dixon retired from his job at a wholesale distributor for heat and cooling supply products and began waiting.

"They gave me the medicine for five or six months and it became toxic to me," said Dixon, who began to suffer from excruciating headaches and lost 30 pounds.

But the medicine was working. Dixon watched his tumor regress, or shrink, "by 50-60 percent" in volume on CT scans.